Cationic Spherical Polypeptides with Immunogenic Cell Death Inducing Activity for Oncolytic Immunotherapy

CCS CHEMISTRY(2024)

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摘要
Immunogenic cell death (ICD) has gained increasing attention due to its capacity to trigger anticancer immunity. Herein, we report a series of fabricated cationic spherical polypeptides (CSPs) designated CSP-0 to CSP-57, with oncolytic activity and ICDinducing ability. CSP-57 exerted the optimal broadspectrum and tumor -cell -selective cytotoxicity by disrupting cell membranes and inducing cell necrosis. Moreover, CSP-57 damaged mitochondrial membranes, thereby elevating intracellular levels of reactive oxygen species, leading to robust ICD of tumor cells featured by multiple damage -associated molecular patterns, including calreticulin, high -mobility group box 1, and adenosine triphosphate. In vivo anticancer activity determination results suggested that CSP-57 significantly delayed B16F10 tumor growth in mice by direct oncolysis and subsequent induction of ICD. The immunotherapeutic efficacy of CSP-57 was characterized by elevated ratios of cytotoxic T cells in tumors and spleens. Briefly, this work indicates that CSPs represent a promising strategy for oncolytic immunotherapy.
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关键词
cationic spherical polypeptides,oncolysis,mitochondrial damage,immunogenic cell death,immunotherapy
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